Preterm delivery is a major health problem in the minority populations in this country. They have' a greater incidence of preterm birth, which is not related to socioeconomic status or prenatal care. The psychosocial costs are high, but the cost in care to the newborns alone is more than $5 billion. The major cause of preterm birth in the Afro-American population is the preterm premature rupture of the fetal membranes. Intrauterine infection is a cause for some but not all of these births, and other idiopathic mechanisms must occur. The goal of this proposal is. to seek localized connective tissue changes preceding the rupture of the human fetal membranes and to determine whether the degree of such changes is related to the differing degrees of premature rupture and birth in four different ethnic groups in Hawaii: Afro-American, Hawaiian, Filipino and Caucasian. The first specific aim is to locaIize connective tissue changes in the fetal membranes by quantitating the gene expression of key collagenolytic enzymes, an activator and a hormone involved in stimulating expression of this system in four zones relative to the position of the placenta. A morphologically distinct zone near the rupture site will be sought by quantitative image analysis and quantitative in situ hybridization histochemistry for the enzymes, activator and hormone involved in pericellular collagenolysis. The second specific aim will quantitate these localized connective tissue changes in four ethnic groups in Hawaii and relate these to the respective incidence of preterm premature rupture of the membranes in these groups. There have been no studies to date using fetal membranes from women representing different ethnic groups or attempts to scientifically explain the remarkable differences in preterm birth due to the preterm premature rupture of these membranes.